Solitary Keratoacanthoma Research Articles

Intralesional methotrexate as non-surgical therapy for giant keratoacanthoma on the nose

Keratoacanthoma is an epithelial tumour derived from hair follicles. Clinical and histopathological features of keratoacanthoma can resemble that of squamous cell carcinoma. Different treatment alternatives have been described over the years including intralesional methotrexate injection. We present an interesting case of treatment of solitary keratoacanthoma lesion on the nose with intralesional methotrexate as non-surgical therapy.

Dyschromatosis universalis hereditaria.

Reticulate pigmentary dyschromatoses primarily include dyschromatosis universalis hereditaria (DUH), dyschromatosis symmetrica hereditaria (DSH) (Reticulate acropigmentation of Dohi), and unilateral dermatomal pigmentary dermatosis, which differ in their patterns of distribution. The disease was initially described by Ichikawa and Hiraga in Germany in 1933. The prevalence of DUH is 0.3 per 100,000 with a female preponderance. The skin lesions usually appear in infancy or early childhood and cease to progress beyond adolescence. The subtypes DUH 1 and DUH 3 are found to have autosomal dominant inheritance, which is the most common inheritance pattern, while DUH 2 has an autosomal recessive pattern. The most common gene involved in DUH is ABCB6, while the other genes include SASH 1, PER 3, and KITLG (DUH type 2). DUH is characterized by multiple irregular hyperpigmented macules interspersed with hypopigmented macules in a mottled pattern over the trunk and extremities. The face is involved in 50% of individuals. Rarely, it can also involve hairs, nails, mucous membranes, palms, and soles. Other varied presentations include localized forms, localization of lesions to sun-exposed areas, large macules, uniform palmar hypopigmentation, diffuse hyperpigmentation with spotty depigmented macules, and unilateral involvement. DUH has been reported to be associated with various cutaneous and systemic diseases. The authors have observed cases of DUH associated with hepatocellular carcinoma, solitary keratoacanthoma, and dermoid cyst. The various diagnostic modalities include dermoscopy, histopathology, electron microscopy, and targeted gene sequencing. Though various treatment modalities like NBUVB and lasers have been tried, no treatment is promising.

Aberrant p16, p53 and Ki-67 immunohistochemistry staining patterns can distinguish solitary keratoacanthoma from cutaneous squamous cell carcinoma

Keratoacanthoma (KA) is widely considered a benign, usually self-resolving, neoplasm distinct from cutaneous squamous cell carcinoma (cSCC), while some consider KA to be indistinguishable from cSCC. Published studies indicate utility for p16, p53, Ki-67 immunostaining and elastic van Gieson (EVG) in the assessment of KA and cSCC. We compared clinical features and staining patterns for p16, p53, Ki-67 and EVG in fully excised KA, cSCC with KA-like features (cSCC-KAL) and other cSCC (cSCC-OTHER). Significant differences between KA, cSCC-KAL and cSCC-OTHER were found for head and neck location (20%, 86%, 84%), and duration <5 months (95%, 63%, 36%). KA shows both a mosaic pattern for p16 (>25-90% of neoplasm area) and peripheral graded pattern for p53 (up to 50% moderate and strong nuclear staining) in 92% compared with 0% of cSCC-KAL and 0% of cSCC-OTHER. In contrast, a highly aberrant pattern (usually null) for one or both p16 and p53, was present in 0% of KA, 83.8% of cSCC-KAL and 90.9% of cSCC-OTHER. Abnormal distribution of Ki-67 beyond the peripheral 1-3 cells was uncommon in KA (4.2%) and common in cSCC-KAL (67.6%) and cSCC-OTHER (88.4%). Moderate to striking entrapment of elastic and collagen fibres was present in the majority of KA (84%), cSCC-KAL (81%) and cSCC-OTHER (65%). KA are clinically distinct neoplasms typically of short duration occurring preferentially outside the head and neck and generally lacking aberrations of p16, p53 and Ki-67, compared with cSCC that have high rates of aberrant or highly aberrant p16, p53 and Ki-67, but EVG lacked specificity.

Solitary Keratoacanthoma at the Recipient Site of a Full-Thickness Skin Graft: A Case Report and Review of the Literature.

A 57-year-old man presented with a pigmented papule, 0.4 cm in diameter, on the left lower eyelid. Skin biopsy revealed a basal cell carcinoma, which was excised through a wide excision followed by a full-thickness skin graft (FTSG). Two weeks after the surgery, an erythematous nodule developed in the lower margin of the graft recipient site. The nodule size increased rapidly over 2 weeks, becoming dome-shaped with a central hyperkeratotic plug. A diagnosis of keratoacanthoma (KA) was made, and surgical excision was performed. Histological findings revealed a large, well-differentiated squamous tumor with a central keratin-filled crater and buttress. The human papilloma virus (HPV) genotyping results were negative. Risk factors for KA include trauma, old age, exposure to ultraviolet (UV) radiation, immunosuppression, and HPV infection. KA has most often been reported to develop at the donor site. Although the pathogenesis of KA is unclear, trauma is believed to act as a second insult to a preceding oncogenic insult, such as exposure to UV radiation, resulting in a koebnerization. Herein, we report a case of solitary KA at a FTSG recipient site. This report presents information that may provide guidance during dermatologic surgeries.

Синдром Мьюир-Торре – предиктор рака желудка (клиническое наблюдение)

Muir-Torre syndrome is a hereditary autosomal dominant syndrome that belongs to HNPCC (Lynch syndrome), being its subspecies. The disease is associated with a high risk of developing colorectal cancer, as well as other cancers of the gastrointestinal tract, genitourinary tract and skin lesions in the form of tumors of the sebaceous glands and keratoacanthus. Visceral cancer in the syndrome is characterized by multiple localization and a low degree of malignancy. Mutations in the genes MSH2 and MLH1 - loci 2p22–p21 and 3p21.3 in the DNA repair system were detected in patients with Muir-Torre syndrome, which leads to its microsatellite instability. Skin tumors may precede visceral cancer, may develop in parallel with the malignant process of internal organs. The importance of timely diagnosis of skin neoplasms (sebaceous gland adenomas and keratoacanthus) as a marker of Muir-Torre syndrome is emphasized. The article presents a clinical case of Muir-Torre syndrome in a 50-year-old patient, which was manifested by a combination of gastric cancer, multiple adenomas of the sebaceous glands and solitary keratoacanthoma. The first manifestations of the syndrome were adenomas of the sebaceous glands of the facial skin, mistakenly regarded by dermatologists as a papular form of rosacea. After 4 years, the patient underwent surgery for a keratoacanthoma of the shin, a couple of months later, the patient was diagnosed with stage IIA gastric cancer (T3N0M0), a ring-cell variant. Skin rashes were regarded as hereditary paraneoplastic Muir–Torre syndrome. In order to detect oncological diseases early, it is necessary to improve the qualifications of doctors in the clinic and diagnosis of hereditary paraneoplastic dermatoses.

Keratoacanthoma seen with hidradenitis suppurativa: A case report

Hidradenitis suppurativa (HS) is considered a primary disease of the hair follicle. The chronic occlusion of the follicular pilosebaceous unit and an associated immune response appears to be the main causes. The chronic, active, and poorly controlled disease may lead to several complications such as scars, contractures, lymphedema, osteomyelitis, and squamous cell carcinoma (SCC). We report here a 33-year-old male with HS who developed keratoacanthoma while on secukinumab treatment. The tumor representing 2 weeks of evolution in an area affected by HS (lower abdomen) was followed up after histopathological confirmation. Almost complete spontaneous regression was observed at the subsequent visits. As far as we are aware, solitary keratoacanthoma associated with HS has not been previously described. Our case shows that squamous differentiation is not limited to SCC and can develop from any scar tissue outside the anogenital region in patients with HS. Thus, the case presented here emphasizes the necessity of careful examination in scar areas as well as inflammatory lesions in HS.

The diagnostic value of imaging techniques for keratoacanthoma: A review

Keratoacanthoma (KA) is a fast-growing skin tumor with solitary KA being the most common type. KAs rarely metastasize and subside spontaneously. Although histopathology is the gold standard for the diagnosis of KA, its histopathological features are sometimes difficult to distinguish from those of other skin tumors. Imaging studies have certain advantages in the preoperative diagnosis of KA; they not only show the exact shape of the lesion but can also accurately determine the extent of the lesion. Combined with histopathological examination, these findings help establish a diagnosis. By summarizing the imaging features of KA, this article aimed to improve radiologists' understanding of the disease and help in the clinical and differential diagnosis of KA.

35328 Morbidities associated with solitary keratoacanthomas

Background: Keratoacanthomas (KA) are classically described as benign tumors that undergo a period of rapid growth followed spontaneously regress several months later. Despite the propensity to naturally regress, most clinicians do not postpone treatment to wait for this to occur. This is likely due to the inability to predict maximal size and potential development of pain and extensive, local destruction and scarring. Some studies have also identified extensive perineural invasion as a complication of KAs.

Multiple eruptive squamoproliferative lesions during anti-PD1 immunotherapy for metastatic melanoma: Pathogenesis, immunohistochemical analysis and treatment.

Treatment with anti-PD1 inhibitors may enhance the risk for developing low grade squamoproliferative skin tumors. Immunohistochemical (IHC) analysis of the immune tumor microenvironment (TME) allows exploration of the pathogenesis and relationship with the PD1/PDL1 axis. Patients with eruptive keratoacanthoma (KA)-like lesions were recruited from the Melanoma Institute Australia, a tertiary referral specialist melanoma treatment center from January 2015 to August 2017. Clinicopathologic evaluation and IHC features of tumor cells (PDL1 expression) and peritumoral microenvironment (PD1, FOXP3, PDL1, CD4:CD8 expressing cells) in 12 eruptive KA-like lesions, were compared with solitary KAs in age and sex matched non-anti-PD1 treated controls. Four patients with repeated episodes of eruptive KA-like and lichenoid lesions developing 2-7 months after commencing pembrolizumab for AJCC stage IV melanoma, were recruited. Eruptive KA-like squamoproliferative lesions occurred in sun exposed sites and in areas of resolving, concomitant or delayed lichenoid reactions. Histologically, the lesions were well-differentiated squamoproliferative lesions resembling infundibulocystic squamous cell carcinoma or KA. IHC of cases and controls revealed low PDL1 expression of both squamous tumor cells and the TME immune cells. The numbers of immunosuppressive FOXP3 positive Tregs and PD1-expressing T-cells were higher in the cases than the controls but the CD4:CD8 ratio (2:1) was similar. The patients best responded to acitretin and were managed surgically if they demonstrated neoplastic features. Accelerated squamoproliferative growth in actinically damaged keratinocytes associated with lichenoid eruptions may be unmasked in patients treated with anti-PD1 immunotherapy potentially contributed to by a local cutaneous immunosuppressed TME.

What Is a Solitary Keratoacanthoma? A Benign Follicular Neoplasm, Frequently Associated with Squamous Cell Carcinoma.

We present histopathological criteria for diagnosing keratoacanthoma (KA). In KA, four histological stages are recognized, which are the early/proliferative stage, well-developed stage, regressing stage and regressed stage. In diagnosing KA, we emphasize that KA consists of the proliferation of enlarged pale pink cells with ground glass-like cytoplasm without nuclear atypia, other than crateriform architecture. KA sometimes exhibits malignant transformation within the lesions. We describe the characteristics of benign and malignant epithelial crateriform tumors that should be differentiated from KA. We also present the data of histopathological diagnosis of lesions clinically diagnosed as KA, its natural course and related lesions after partial biopsy, and incidence of crateriform epithelial neoplasms. Based on these data, we recommend complete excision of the lesion when KA is clinically suspected, especially when the lesion is located on a sun-exposed area of an elderly patient. If complete excision is impossible, partial excision of a sufficient specimen with intact architecture is required. In such a case, however, careful investigation after biopsy will be needed, even if the histopathological diagnosis is KA, because there is some possibility that a conventional SCC lesion remains in the residual tissue.

Successful Treatment of Generalized Eruptive Keratoacanthoma of Grzybowski with Acitretin.

IntroductionKeratoacanthomas (KA) are common cutaneous skin tumors originating from the hair follicles. Unlike squamous cell carcinoma, KA can regress spontaneously and have a benign evolution. Solitary KA is the most common form but familial multiple KA (Ferguson–Smith type), genetically predisposed KA (such as in xeroderma pigmentosum, or Muir–Torre syndrome), or sporadic multiple eruptive KA (Grzybowski type) have been described. Generalized eruptive KA of Grzybowski (GEKA) is a rare condition (around 40 reported cases). The pathophysiology is still unclear. Human papillomavirus (HPV) has been detected in sporadic KA but the presence of HPV39 has never been reported, to our knowledge, in GEKA.Case ReportGEKA in an 80-year-old woman was successfully treated with acitretin (0.5 mg/kg/day) combined with surgical removal of the largest lesions. Treatment was well tolerated and led to decreased pruritus and tumor regression within 6 months. The presence of HPV39 was detected in a lesion by polymerase chain reaction and Sanger sequencing. No genetic alteration was found, in particular in the genes usually altered in squamous cell carcinoma (including NOTCH1, NOTCH2, CDKN2A, TP53).ConclusionWe report a case of GEKA associated with the presence of HPV39 and the successful use of acitretin combined with surgical removal of the larger lesions.

Solitary keratoacanthoma of the lip vermilion: case report and comprehensive review of literature

Solitary keratoacanthoma of the lip vermilion: case report and comprehensive review of literature

Solitary keratoacanthoma resolved after a single intralesional 5-fluorouracil therapy

Solitary keratoacanthoma resolved after a single intralesional 5-fluorouracil therapy

Clinicopathological study of crateriform verruca: Crateriform epithelial lesions histopathologically distinct from keratoacanthoma.

Keratoacanthoma (KA) is a distinct clinicopathological entity, but it is often confused with other crateriform tumors. This study re-examined the clinicopathological features of 380 crateriform epithelial tumors with a central keratin plug. Seventy-six tumors (20%) had histopathological features that differed from solitary KA and were more verruca-like, and we designated these lesions as crateriform verruca (CFV). We performed clinicopathological re-examination of these neoplasms with a crateriform architecture and epithelial lip-like structures similar to KA, which also displayed histopathological features reminiscent of verruca vulgaris, such as finger-like exophytic projections with hyperkeratosis and acanthosis, focal hypergranulosis and arborization. Clinical data on CFV were also summarized. The main histopathological differences from KA were that CFV showed proliferation of keratinocytes with a similar size and regular arrangement, and the base of CFV was well demarcated without endophytic growth. Interestingly, some CFV were partly composed of epithelial cells with large pink cytoplasm in the upper malpighian layer between papillomatous projections. Furthermore, areas of trichilemmal-like keratinization without formation of the granular layer were seen in some lesions. These types of CFV were hardly distinguishable from KA, unless it is recognized that CFV may contain trichilemmal keratinization-like areas accompanied by large epithelial cells with eosinophilic cytoplasm. We have proposed the term CFV for these verrucous neoplasms to differentiate them from KA.

Eruptive keratoacanthomas after radiation therapy for keratoacanthoma centrifugum marginatum

Keratoacanthomas are crateriform squamous proliferations commonly accepted as a variant of well-differentiated squamous cell carcinoma (SCC). Typically, keratoacanthomas demonstrate rapid growth that causes local tissue destruction followed by spontaneous resolution with residual scarring. There are several morphological variants of keratoacanthomas, including solitary, multiple, grouped, and keratoacanthoma centrifugum marginatum (KCM). KCM is characterized by progressive peripheral tumor expansion with the ability to grow up to 30 cm in diameter. Because of their destructive capabilities and rare reports of metastasis, [1] Hodak E. Jones R.E. Ackerman A.B. Solitary keratoacanthoma is a squamous-cell carcinoma: Three examples with metastases. Am J Dermatopathol. 1993; 15: 332-342 Crossref PubMed Scopus (206) Google Scholar keratoacanthomas require definitive treatment.

Generalized eruptive keratoacanthoma: proposed diagnostic criteria and therapeutic evaluation.

Generalized eruptive keratoacanthoma (GEKA) of Grzybowski is a sporadically occurring, extremely rare variant of keratoacanthoma characterized clinically by severely pruritic, generalized eruption of numerous small follicular papules, often with a central keratotic plug, and histologically by typical features of solitary keratoacanthoma. Despite the continuous addition of new case reports, no definite diagnostic criteria have been established, and an optimum treatment is not yet determined. Herein, we review the different aspects of this rare entity, including pathogenesis, clinical and histopathological features, differential diagnosis, course and prognosis. Different therapeutic approaches and their impact on the course and prognosis of the disease are also evaluated and presented. We propose two sets of diagnostic criteria to define the disease more precisely and to avoid overlapping and confusion with other types of multiple keratoacanthoma. The first set comprises constant clinical and histopathological features that almost always present in every case and the second set includes variable features that were reported in some patients, and to which any emerging finding could be added to avoid missing cases. Although different therapeutic options have been used, either as single agents or in combinations, there is no standard therapy for GEKA and the disease still represents a therapeutic challenge.

Keratoacanthoma centrifugum marginatum at an unusual site

Keratoacanthoma (KA) is a rapidly evolving tumor, composed of keratinizing squamous cells originating in pilosebaceous follicles and resolving spontaneously if left untreated. It is relatively uncommon in dark-skinned and occurs in middle aged individuals. Males are three times more affected than females. It presents as firm, rounded, flesh-colored or reddish papule; with a rapid growth phase followed by spontaneous healing over three months. Two types of KA exist i.e., solitary and multiple. There are three rare clinical variants of solitary KA, namely giant KA, keratoacanthoma centrifugum marginatum (KCM) and subungual KA. In KCM, lesions are large, reaching upto 20cms. There is peripheral extension with raised, rolled border and atrophy in the center. There is no tendency toward spontaneous involution. The most common locations are dorsa of hands and legs, lesions on scalp being rare. A rare case of KCM occurring on scalp which is an unusual site is reported.

Efficacy of topical photodynamic therapy for keratoacanthomas: A case-series of four patients

Topical photodynamic therapy (PDT) is an excellent treatment option for various non-melanoma skin cancers and precancerous lesions, including actinic keratosis, Bowen's disease, and basal cell carcinoma. The clinical use of PDT includes a broad range of neoplastic, inflammatory, and infectious skin diseases. There is also anecdotal evidence suggesting the efficacy of PDT for the treatment of keratoacanthomas (KA). We report a case-series of four patients with solitary KA confirmed by histology, treated with topical PDT with methylaminolevulinic acid (MAL) cream. After three sessions of PDT, the lesions completely disappeared. There was no evidence of recurrence and excellent cosmetic outcome was achieved after three years of follow-up. Topical photodynamic therapy with MAL can be a therapeutic alternative for KA with good clinical and cosmetic outcomes.

Solitary keratoacanthoma involving upper lip: a diagnostic dilemma - case report and a brief review

Keratoacanthoma (KA) is a benign epithelial proliferative lesion which frequently occurs on the sun exposed areas of the skin. KA originates within the pilosebaceous apparatus of the skin and may be solitary or multiple. Solitary KA can be difficult to differentiate from squamous cell carcinoma (SCC) both clinically and microscopically. However, the clinical course of the lesion and its ability to self involute makes it a distinct clinical entity. Solitary KA appears on the vermilion border of the lower lips with some frequency. A case of keratoacanthoma involving the upper lip is reported presenting as an exophytic growth that resolved after excisional biopsy. Photographic documentation of the case along with relevant management protocol is discussed. The article emphasizes the significance of recognizing such lesion and discriminating it from SCC thus carrying diagnostic and therapeutic implications. However, in case of dilemma it is prudent to assume that the lesion is SCC unless proved otherwise clinically or histologically.

A case of Ferguson–Smith type multiple keratoacanthomas associated with keratoacanthoma centrifugum marginatum: response to oral acitretin

Keratoacanthoma centrifugum marginatum (KCM) is a rare entity, usually classified as solitary keratoacanthoma (KA). The Ferguson-Smith type is the most common form of multiple KAs. Because development of multiple KAs and KCM in a single patient has rarely been reported, this association presents a therapeutic challenge. We report a 46-year-old man with Ferguson-Smith multiple KAs and KCM, who was successfully treated with acitretin.